RESUMO
BACKGROUND: Fetal exposure to maternal ingestion of warfarin is known to produce certain dysmorphic features in the neonate, known as fetal warfarin syndrome (FWS). There is a general consensus that maternal intake of warfarin at a daily dose of 5 mg or less is safe both for the infant and the mother. METHODS: We report four cases of FWS born to mothers with rheumatic heart disease on warfarin prophylaxis during pregnancy at a dose less than 5 mg/day. RESULTS: Along with typical facial features of FWS and multiple epiphyseal stippling in skeletal x-ray, Case 1 had Dandy-Walker malformation and Case 2 had laryngo-tracheomalacia and patent ductus arteriosus. CONCLUSION: We emphasize the need for optimizing the choice and dosage schedule of anticoagulants during pregnancy, least harmful for the mother and her developing fetus.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Anticoagulantes/efeitos adversos , Osso Nasal/anormalidades , Efeitos Tardios da Exposição Pré-Natal , Varfarina/efeitos adversos , Anormalidades Múltiplas/induzido quimicamente , Adulto , Síndrome de Dandy-Walker/induzido quimicamente , Permeabilidade do Canal Arterial/induzido quimicamente , Feminino , Próteses Valvulares Cardíacas , Humanos , Osso Nasal/patologia , Gravidez , Cardiopatia ReumáticaAssuntos
Antirretrovirais/efeitos adversos , Síndrome de Dandy-Walker/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Adulto , Antirretrovirais/administração & dosagem , Feminino , Ventrículos do Coração/anormalidades , Humanos , Recém-Nascido , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Masculino , Nevirapina/administração & dosagem , Nevirapina/efeitos adversos , Gravidez , Estavudina/administração & dosagem , Estavudina/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversosAssuntos
Doenças do Sistema Nervoso Central/induzido quimicamente , Doenças do Sistema Nervoso Central/epidemiologia , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Baltimore , Benzoxazinas , Ciclopropanos , Síndrome de Dandy-Walker/induzido quimicamente , Síndrome de Dandy-Walker/epidemiologia , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Humanos , Recém-Nascido , Corpo Clínico Hospitalar , Oxazinas/administração & dosagem , Oxazinas/efeitos adversos , Oxazinas/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêuticoAssuntos
Anormalidades Induzidas por Medicamentos/diagnóstico , Infecções por HIV/tratamento farmacológico , Oxazinas/efeitos adversos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/epidemiologia , Alcinos , Benzoxazinas , Ciclopropanos , Síndrome de Dandy-Walker/induzido quimicamente , Síndrome de Dandy-Walker/diagnóstico , Feminino , Monitorização Fetal/métodos , Seguimentos , Humanos , Recém-Nascido , Meningomielocele/induzido quimicamente , Meningomielocele/diagnóstico , Monitorização Fisiológica/métodos , Oxazinas/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/virologia , Primeiro Trimestre da Gravidez , Estudos RetrospectivosRESUMO
Morphological and developmental changes of the ventricular system are analyzed in three major experimental models of congenital hydrocephalus in the rat: 6-aminonicotinamide (6-AN)-induced and LEW/Jms and HTX mutant hydrocephalus. The clinically comparable forms of hydrocephalus and problems occurring during each period of intrauterine hydrocephalus are then discussed. Comparative morphological study revealed that 6-AN-induced hydrocephalus was comparable to the Dandy-Walker syndrome and that the critical period regarding this syndrome in fetal life was at the time of "legal termination". The LEW/Jms and HTX mutant models were identical with regard to the form of progressive hydrocephalus in the postnatal period, but the condition underlying the hydrocephalus during the fetal period differed. The LEW/Jms model was comparable to primary congenital aqueductal stenosis (aqueductal agenesis), and the hydrocephalic state appeared in the period of "intrauterine preservation" before pulmonary maturation was completed. On the other hand, the HTX fetuses demonstrated secondary change of the aqueduct in the perinatal period, although the model was considered to be of congenital communicating hydrocephalus. Cerebrospinal fluid (CSF) dynamics studied in the fetuses with 6-AN-induced hydrocephalus disclosed considerable pathophysiology comparable to "hydromyelic hydrocephalus." The historical trends of animal experimental models of congenital hydrocephalus are reviewed and comparable clinical problems suggested by those models discussed further.
Assuntos
Síndrome de Dandy-Walker/embriologia , Síndrome de Dandy-Walker/patologia , Modelos Animais de Doenças , 6-Aminonicotinamida , Animais , Aqueduto do Mesencéfalo/anormalidades , Aqueduto do Mesencéfalo/patologia , Ventrículos Cerebrais/embriologia , Ventrículos Cerebrais/patologia , Constrição Patológica , Síndrome de Dandy-Walker/induzido quimicamente , Síndrome de Dandy-Walker/genética , Feminino , Masculino , Mutação , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-DawleyRESUMO
While the warfarin embryopathy is well defined, central nervous system abnormalities associated with gestational warfarin exposure require further definition. Based on the timing of warfarin exposure in humans, it has been proposed that second- and third-trimester exposure predisposes to CNS abnormalities while first-trimester exposure more typically is associated with the warfarin embryopathy. A case is presented of a liveborn male with Dandy Walker malformation, agenesis of the corpus callosum, and Peter anomaly of the right eye who was exposed to warfarin between the 8th and 12th weeks of gestation who had none of the stigmata of the warfarin embryopathy. His is the first known case of exposure confined to the first trimester, and the fifth case of Dandy Walker malformation among a total of 15 CNS cases associated with this drug. This case offers evidence that Dandy Walker malformation may represent a distinct complication of in utero first-trimester exposure, and consideration of these particular abnormalities with exposure limited to a period prior to the known appearance of vitamin K-dependent clotting factors suggests that warfarin has a direct teratogenic effect on central nervous system morphogenesis.